Preparation method for improving purity of terbinafine hydrochloride

Abstract

The invention discloses a preparation method for improving the purity of terbinafine hydrochloride, and the method comprises the following steps: 1) adding an acid binding agent into water, stirring and dissolving, adding N-methylnaphthylamine and 1-chlorine-6,6-dimethyl-2-heptene-4-alkyne, and cooling to room temperature; adding ethyl acetate for extraction, filtering, adding a hydrochloric acidaqueous solution, stirring, and filtering to obtain crude terbinafine hydrochloride; and 2) purifying the terbinafine hydrochloride, namely adding the crude terbinafine hydrochloride in the step 1) and purified water into a reaction kettle, heating and refluxing to dissolve, cooling to room temperature, and filtering to obtain a finished product of the terbinafine hydrochloride. According to the preparation method of the terbinafine hydrochloride, only water is used as a crystallization solvent and no toxic solvent is used in the final step reaction of the bulk drug, so that potential harm oftoxic organic solvents to human bodies is avoided; moreover, the solvent amount is extremely small, the cost is low, the generated waste liquid is less, the pollution to the environment is reduced, the product purity and yield are high, the reaction operation is simple, the control is easy, the production period is short, and commercial production is facilitated.

Description

technical field [0001] The invention relates to a synthesis of terbinafine hydrochloride, in particular to a preparation method for improving the purity of terbinafine hydrochloride. Background technique [0002] Terbinafine hydrochloride can be used to treat skin, hair and nail infections caused by Trichophyton, Microsporum canis and Epidermophyton flocculum, etc. It can also treat various ringworm diseases and skin yeast infections caused by Candida, and onychomycosis caused by mold fungi. Terbinafine hydrochloride is an allylamine antifungal drug, which inhibits squalene cyclooxygenase in the process of ergosterol synthesis in fungal cells, and makes squalene accumulate in cells to play a bactericidal effect. [0003] At present, the synthetic method of the final step of terbinafine hydrochloride bulk drug basically all adopts naphthylmethylamine and 1-chloro-6,6-dimethyl-2-hepten-4-yne one-step reaction obtains, but aftertreatment and Purification methods are all cumbe...

AI Technical Summary

Problems solved by technology

[0004] The technical problem to be solved by the present invention is that the last step synthetic method of existing terbinafine hydrochloride usually adopts the organic solvent to crystallize, the production cost is high and the product purification is difficult, and some organic solvents have certain toxicity and pollute the environment. The purpose is to A preparation method for improving the purity of terbinafine hydrochloride is provided. In the final refining process of raw materials, only water is used as the crystallization solvent, no toxic solvent is used, and the potential harm of toxic organic solvents to the human body is avoided, and the amount of solvent is extremely small , low cost, less waste liquid generated, reduced environmental pollution, high product purity and yield, simple reaction operation, easy control, short production cycle, and conducive to commercial production

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